Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carcinoma
Estrogen receptor-binding fragment-associated antigen 9 is a tumor-promoting and prognostic factor for renal cell carcinoma
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DOI：
10.1158/0008-5472.can-04-3497
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发表时间：
2005-05-01
期刊：
影响因子：
11.2
通讯作者：
Inoue, S
中科院分区：
文献类型：
--
作者：
Ogushi, T;Takahashi, S;Inoue, S
雌激素受体结合片段相关抗原9（EBAG 9）已被确定为人乳腺癌MCF 7细胞中的主要雌激素应答基因。在浸润性乳腺癌和晚期前列腺癌中观察到EBAG 9的高表达，表明该蛋白在恶性肿瘤中具有促肿瘤作用。在这里，我们表明，肿瘤内（i.t.）施用针对EBAG 9的小干扰RNA在皮下给药后产生明显的肿瘤消退。移植鼠肾细胞癌（RCC）Renca细胞。EBAG 9的过表达没有促进培养的Renca细胞的增殖;然而，与单独表达载体的Renca细胞（Rencavector）相比，接种的携带EBAG 9的Renca细胞（Renca-EBAG 9）在BALB/c小鼠中生长更快，并形成更大的肿瘤。肾包膜下移植后，Renca-EBAG 9肿瘤与BALB/c小鼠中的Renca载体肿瘤相比显著增大，而Renca-EBAG 9和Renca载体肿瘤在BALB/c裸鼠中以相似的体积发展。在针对Renca-EBAG 9和Renca载体细胞的特异性细胞毒性T细胞应答中未观察到明显差异;尽管如此，在Renca-EBAG 9包膜下肿瘤中浸润的CD 8 + T淋巴细胞的数量减少。此外，EBAG 9在78例肾癌组织中的免疫组化研究显示，在87%的病例中观察到强烈和弥漫的胞浆免疫染色，EBAG 9阳性与患者的不良预后密切相关。多因素分析显示，EBAG 9高表达是疾病特异性生存的独立预后预测因子（P = 0.0485）。我们的研究结果表明EBAG 9是肿瘤进展的重要调节因子，也是RCC的潜在预后标志物。
The estrogen receptor-binding fragment-associated antigen 9 (EBAG9) has been identified as a primary estrogen-responsive gene in human breast cancer MCF7 cells. A high expression of EBAG9 has been observed in invasive breast cancer and advanced prostate cancer, suggesting a tumorpromoting role of the protein in malignancies. Here we show that intratumoral (i.t.) administration of small interfering RNA against EBAG9 exerted overt regression of tumors following s.c. implantation of murine renal cell carcinoma (RCC) Renca cells. Overexpression of EBAG9 did not promote the proliferation of culture Renca cells; however, the inoculated Renca cells harboring EBAG9 (Renca-EBAG9) in BALB/c mice grew faster and developed larger tumors compared with Renca cells expressing vector alone (Rencavector). After renal subcapsular implantation, Renca-EBAG9 tumors significantly enlarged compared with Renca-vector tumors in BALB/c mice, whereas both Renca-EBAG9 and Renca-vector tumors were developed with similar volumes in BALB/c nude mice. No apparent difference was observed in specific cytotoxic T-cell responses against Renca-EBAG9 and Renca-vector cells; nonetheless, the number of infiltrating CD8+ T lymphocytes was decreased in Renca-EBAG9 subcapsular tumors. Furthermore, immunohistochemical study of EBAG9 in 78 human RCC specimens showed that intense and diffuse cytoplasmic immunostaining was observed in 87% of the cases and positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients. Multivariate analysis revealed that high EBAG9 expression was an independent prognostic predictor for disease-specific survival (P = 0.0485). Our results suggest that EBAG9 is a crucial regulator of tumor progression and a potential prognostic marker for RCC.